Oxidized low density lipoprotein (LDL) may be of central importance in triggering atherosclerosis. One potential pathway involves the production of nitric oxide (NO) by vascular wall endothelial cells and macrophages. NO reacts with superoxide to form peroxynitrite (ONOO-), a potent agent of LDL oxidation in vitro. ONOO- nitrates the aromatic ring of free tyrosine to produce 3-nitrotyrosine, a stable product. The detection of 3-nitrotyrosine in LDL isolated from vascular lesions by isotope dilution mass spectrometry raises the possibility that NO, by virtue of its ability to form reactive nitrogen intermediates, may promote atherogenesis, counteracting the well-established anti-atherogenic effects of NO.